An adjuvant is an agent administered to potentiate the immune response to an antigen and/or modulate it toward a desired immune response. An endogenous adjuvant is a compound or molecule naturally occurring within the cell or tissue that likewise enhances an immune response by stimulating innate immunity, thus possessing the capacity to potentiate an effect of some triggering event or agent. Endogenous adjuvants play a central role in alerting the immune system to potential danger and promote response to infection, transplantation, tumor, and autoimmunity.
Vaccines attempt to safely elicit an immunity to pathogens that is ideally robust, protective and long-lived. However, current formulations of many subunit vaccines provide weaker and shorter-lived immunity than natural infection. While it is clear that adjuvants can be used to boost immunity, the adjuvants that are currently approved for use in licensed vaccines are limited. Alum, a mixture of aluminum salts, was the first vaccine adjuvant that was widely utilized in vaccine preparations. Alum is a weak adjuvant and one that biases responses to effector responses (Th2) that are not protective against many pathogens. It was the only vaccine adjuvant in use in the United States until 2009, when the U.S. Food and Drug Administration approved Cervarix, a human papillomavirus vaccine that contains an adjuvant designated as AS04. This adjuvant is a mixture of alum and a bacterial lipid (fat) molecule that has been modified so that it does not cause disease.
Endogenous adjuvants generally have not been evaluated for their potential use in vaccines. In theory, they may allow vaccinations to safely mimic the pathway that naturally triggers immunity to many pathogens. These agents also promote CD8+ T cell immune responses which are important to developing immunity to many pathogens such as viruses and tumors but which are not elicited by most subunit vaccines (Rock et al. in Springer Seminars in Immunopathology (2005) 26:231-246).
Clearly, identification of endogenous adjuvants, triggered in response to certain pathogens, may provide novel exogenous adjuvants, which may thereafter be administered exogenously to enhance an immune response and augment the potency of vaccines and cancer immunotherapies.